Field of the Invention
The present invention relates to mixing and filtering systems such as for separating cells from a fluid medium or for separating cells from micro carriers suspended in a fluid medium.
Description of the Related Art
In the field of culturing cells for biological and/or chemical use or testing and/or other reasons, cells are grown in a culture fluid or on micro carriers suspended in a fluid medium. The cells must then be separated from debris such as dead cells and/or from the micro carriers. An aseptic mixing and filtering system is used to isolate healthy cells. These cells may be used for many purposes, for example for vaccines, for testing for vaccines, for testing for viruses, enzymes, synthetic hormones, and other products of biotechnology.
The cells are separated by putting a culture with cells and/or cells on micro carriers into an aseptic tank with a mixing and filtering system. When separating cells from a fluid medium or from micro carriers suspended in a fluid medium, it is important to achieve complete mixing and filtering or as complete as possible to obtain the highest concentration of cells. It is also important not to mix too harshly, so that cells do not get damaged. Further, it is important to use equipment that is inert and that is easily cleaned and sterilized so the aseptic environment may be maintained. The presence of dead cells and/or unhealthy cells (generally smaller than healthy cells) can substantially hinder and slow down the process of achieving a concentration of fresh, healthy cells for maximum biological effectiveness.
Many mixing and filtering systems can leave a lot of healthy cells unfiltered and/or let too much debris stay with the healthy cells. Mixing and filtering systems can also be difficult to place inside a hermetically sealed vessel or container without comprising the aseptic environment.
The mixing and filtering system normally includes a vessel or container, a tube usually inserted through an opening at the top of the vessel (e.g., through a sealing cap of the vessel), a filter assembly and a mixing assembly. The tube forms a diptube used to remove debris or to remove healthy cells, depending on which is being filtered out of the medium. Therefore, the tube will normally have an opening as close to the bottom of the vessel as possible however it will remain contained behind the barrier of the filter assembly.
Mixing assemblies may have an external drive and a mechanical coupling. However, in such case, the vessel cannot be truly aseptic. A type of mixing assembly that provides internal drive and is therefore aseptic is a magnetic stirrer or mixer. There is a magnet or magnets in the form of a stir bar or other magnetic arrangement inside the vessel. A magnetic stir plate is located outside of the vessel but as close as possible to the magnet(s) inside the vessel. The stir plate has a movable or changeable magnetic field that attracts and repels the magnet(s) inside the vessel in such a way that the magnet(s) inside the vessel rotate(s).
Several U.S. patents are examples of using magnetic mixing in a mixing and filtering system in a vessel. U.S. Pat. No. 4,639,422 to Geimer discloses a mixing vessel having a central tube, vanes and magnetic mixing where the magnet is located below the bottom of the vanes. The vanes appear to be located inside the outer diameter of a filter.
U.S. Pat. No. 4,649,118 to Anderson discloses a mixing device with a central magnet.
U.S. Pat. No. 5,126,269 to Fike et al, U.S. Pat. No. 3,647,632 to Johnson et al, and U.S. Pat. Nos. 4,184,916 and 4,289,854 to Tolbert all disclose a mixing device using a stir bar.
U.S. Pat. No. 6,593,128 to Kiy et al discloses a magnetic mixing device with a magnetic follower.